Saccharide-RNA recognition in a complex formed between neomycin B and an RNA aptamer
Saccharide-RNA recognition in a complex formed between neomycin B and an RNA aptamer
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DOI：
10.1016/s0969-2126(99)80105-1
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发表时间：
1999-07-15
期刊：
影响因子：
5.7
通讯作者：
Patel, DJ
中科院分区：
文献类型：
--
作者：
Jiang, LC;Majumdar, A;Patel, DJ
背景：氨基糖苷类抗生素可以靶向具有微摩尔亲和力的RNA折叠，并抑制从蛋白质生物合成到核酶作用和病毒复制的生物过程。利用化学、生化、光谱学和计算方法对天然RNA靶点和体外筛选鉴定的RNA适体进行了氨基糖苷类抗生素RNA识别的具体特征研究。我们之前对妥布霉素-RNA适配体复合物的研究扩展到新霉素B与其选定的RNA适配体结合，具有100 nM的亲和力。结果：新霉素B的neamine部分（环I和环II）夹在一个“拉链”G.U错配对齐片段的主槽底和一个环出嘌呤碱基之间，该碱基在结合的抗生素上翻动。在新霉素B的带电胺与碱基错配边和主磷酸之间观察到特定的分子间氢键。这些相互作用将2-脱氧链胺环I和吡喃糖环II固定在rna结合袋内。结论：妥布霉素和新霉素B的RNA适体复合物利用共同的结构原理为结合的氨基糖苷类抗生素生成RNA结合袋。在每种情况下，2-脱氧链胺环I和附着的吡喃糖环被封装在主凹槽结合口袋中，该凹槽结合口袋内衬不匹配对。袋内的结合抗生素被一个环出的碱基覆盖，并通过涉及抗生素的带电胺基的分子间氢键固定在适当的位置。
Background: Aminoglycoside antibiotics can target RNA folds with micromolar affinity and inhibit biological processes ranging from protein biosynthesis to ribozyme action and viral replication. Specific features of aminoglycoside antibiotic-RNA recognition have been probed using chemical, biochemical, spectroscopic and computational approaches on both natural RNA targets and RNA aptamers identified through in vitro selection. Our previous studies on tobramycin-RNA aptamer complexes are extended to neomycin B bound to its selected RNA aptamer with 100 nM affinity.Results: The neamine moiety (rings I and II) of neomycin B is sandwiched between the major groove floor of a 'zippered-up' G.U mismatch aligned segment and a looped-out purine base that flaps over the bound antibiotic. Specific intermolecular hydrogen bonds are observed between the charged amines of neomycin B and base mismatch edges and backbone phosphates. These interactions anchor 2-deoxystreptamine ring I and pyranose ring II within the RNA-binding pocket.Conclusions: The RNA aptamer complexes with tobramycin and neomycin B utilize common architectural principles to generate RNA-binding pockets for the bound aminoglycoside antibiotics. In each case, the 2-deoxystreptamine ring I and an attached pyranose ring are encapsulated within the major groove binding pocket, which is lined with mismatch pairs. The bound antibiotic within the pocket is capped over by a looped-out base and anchored in place through intermolecular hydrogen bonds involving charged amine groups of the antibiotic.